During long-distance flights, an increasing number of people suffering from acute thrombophilia are being transported nowadays, and the risk of contracting a thrombosis must not be underestimated. This risk arises if a person is sitting over an extremely long period of time in cramped conditions and additionally suffers from peripheral circulatory disturbances. So far, the only acknowledged prior art method minimising this risk consists in injecting a heparin preparation (usually low-molecular-weight heparin) prior to the start. Since, however, an injection entails other and new risks and is not only complicated but also quite unpleasant for the respective passengers, this preventive measure is applied quite seldom.
It has been found out that low-molecular-weight heparin can in principle also be administered by inhalation. Thus, a preventive effect can be achieved in the blood. However, low-molecular-weight heparin has not yet been administered in practice via inhalation since the exact dosage has not yet been determined in connection with inhalation; however, dosage is a critical aspect with this drug.
So far, the dosage of drugs in form of aerosols in inhalation therapy mainly fails on account of the patient's coordination problems and his/her breathing manoeuvre. This term describes a patient's respiratory depth and rate, how many breaths a patient takes and at which point in time during the inhalation the drug is released when a patient takes a breath. A further aspect that has to be taken into account consists in the physical properties of the aerosol, i.e. the size of the aerosol particle to be inhaled, any hygroscopic properties or electrostatic forces etc. In order to be able to accurately determine the dosage of a drug, it is necessary to know the secretion characteristics of the individual compartments of the respiratory tract. The respective parameter for guaranteeing the drug dosage into the lung then have to be selected on the basis of these characteristics. In the aforementioned case with heparin, the active ingredient has to enter the lung deeply so as to reach the air/blood barrier of the alveoli. Only then can heparin get into the blood where the intended effect is achieved.
Both an over- and an underdosage of an active ingredient is problematic. An underdosage is critical since in the case of heparin thrombosis is not effectively prevented and the aforementioned risks are not eliminated. If, however, an active ingredient, such as heparin is overdosed, there is a danger of internal and external haemorrhage on account of the reduced clotting power of the blood.
In practice, the following problems occur when drugs are administered in form of aerosols:    1. Many very obstructive patients are no longer capable of developing the necessary respiratory flow which they would, however, have to develop for an optimal aerosol application;    2. Many of these patients have only very restricted tidal volumes, above all patients with pulmonary emphysema or patients with very small lung volumes;    3. Every patient inhales at a different rate and with a different volume so that the drug dosage within the lung varies widely.
The present invention relates to the inhalation of heparin as well as other active ingredients. The substitution therapy for drug addicts bears a similar problem. Replacement drugs have so far also been administered in the form of injections although an inhalation would be more effective and would moreover reduce the risks of infections.
EP-A-0 587 380 describes a drug delivery arrangement that recognizes an inhalation and administers the drug only during an inhalation phase of the breathing cycle while the patient is free to breathe as he/she likes. This freedom moreover varies from patient to patient, so that the dosages vary considerably. As regards its practicability, this drug delivery arrangement is for example unsuitable for the administration of heparin as a measure for preventing thrombosis for example during long-distance flights since every patient has to take it along, which is quite inconvenient.
The dosage of the therapeutic aerosols to be inhaled has so far been quite inaccurate and strongly dependent on the, biological morphometry and geometry. Moreover, this dosage is strongly influenced by the patient's individual breathing manoeuvre. In the worst case, the active ingredients do not at all reach the part of the lung to which the drug is to be administered. A further disadvantage is that another inspiration—even of the same patient—results in an overdosage of the active ingredient. Whereas the physical aerosol properties can, as a rule, easily be controlled and are reproducible, the parameters that depend on the patient cannot be controlled at all.
A simple hand-held device setting free a dose of a dry powder or spray is disadvantageous in that individual dosage is impossible. This can only be achieved by a complicated individual inhalation system. The patient can, however, also get an overdosage by inhaling too many doses, and, moreover, he/she would have to take the device along for example in case of long-distance flights since he/she also requires it for the homeward flight. The respective costs are tremendous since every patient requires his/her own device.
In contrast, it is the object of the present invention to provide an improved device for an individual controlled inhalation of therapeutic aerosols, which device is available to a large number of patients despite the achieved individuality. This object is achieved by the features of the claims.
The present invention provides a stationary device for the individual controlled inhalation of therapeutic aerosols. This stationary device comprises at least one drug reservoir so that one or more active ingredients can be offered to the user. Moreover, the stationary device comprises a drug-release means which preferably consists of a pump, a metering means and a disperser. Moreover, a reader for reading a memory means is provided; in this memory means, the patients' individual parameters and/or the aerosol parameters for the inhalation are stored. According to a preferred embodiment, a patient's individual parameters are stored in a memory means that is available under the designations SmartCard, FlashCard or SmartLabel. The individual parameters are stored in the memory means for example upon a measurement of the current pulmonary function of the patient (carried out e.g. by the family doctor). The patient carries along this memory means and, in case of need, inserts it into the respective stationary device according to the invention. Moreover, the stationary device according to the invention comprises a control unit that is connected to the drug-release means and the reader. The control unit triggers the drug-release means as a function of the individual patient and/or aerosol parameters stored in the memory means and provides the patient with the appropriate aerosol dose from the drug reservoir. A first flow (atomiser flow) for the aerosol and, if any, a second flow (auxiliary flow) of additional air supplied to the atomiser flow are generated. The patient inhales this dose. Since it is known that the aerosol deposition in certain areas of the lung depends on the particle size of the active ingredient, the tidal volume and the respiratory flow, the aerosol deposition in the lung can thus essentially be predetermined and exactly controlled. The patient experiences the controlled breathing manoeuvre as pleasant since it is adapted to his/her individual needs.
Preferably, each of the patient's breathing manoeuvres currently carried out with the inhalation apparatus is stored in the memory means that has been inserted into the inhalation apparatus during the inhalation so that the administration can be controlled and the lung may be re-characterised when a certain time of the therapy has lapsed.
In a further preferred embodiment, the memory means is moreover reprogrammable in order to adapt the parameters for a correct breathing manoeuvre to any changes in the pulmonary function of the patient.
Preferably, the inhalation apparatus according to the invention prevents an overdosage, for example by presetting an action period or an action blockage, e.g. in the memory means. This prevents the re-activation of the stationary inhalation apparatus according to the invention by the patient as long as the necessary period of time between two successive inhalations has not lapsed.
In a further preferred embodiment, the inhalation apparatus according to the invention takes into account the pharmacokinetics of the administered drug, i.e. the time necessary for dissimilating the drug. Heparin is, for example, completely dissimilated within three days. If a person inhaled heparin with the inhalation apparatus according to the invention before embarking on a flight and set off on the next flight (return flight) only two days later, the heparin would not be completely dissimilated and merely a minimal dose should be administered. In order to achieve this, the pharmacokinetics of the drug is also stored in the storage means and read out by the reader together with the other parameters.
Preferably, the memory means also serves for recording errors. It records for example whether the atomiser pressure deviates too much from a desired range or whether the required atomiser pressure could not be built up at all. Moreover, the memory means preferably records any safety cutoff when the pressure at the mouthpiece (positive pressure respiration) gets too high. In a further preferred embodiment, a too high deviation of the flow (either the atomiser flow of the aerosol or the auxiliary flow of the additional air supplied to the aerosol air or the sum of both flows) is recorded or an error message if one of the aforementioned flows for the inhalation could not be built up. Preferably, a termination of the inhalation by the patient is also recorded.
The stationary apparatus according to the invention for an individual controlled inhalation of therapeutical aerosols offers the following advantages:    1. Very accurate and individual dosage is possible;    2. Therapy is always available when required (for example for outward and return flights);    3. No individual apparatus has to be carried along;    4. Drug and patient individualisation is possible on account of the reprogrammable memory means;    5. Multiple dosages are prevented by the memory means;    6. Overdosage in case of inhalations rapidly succeeding one another are prevented by taking the pharmacokinetics into account.    7. Different drugs of different manufacturers may be provided and administered by the stationary apparatus;    8. The breathing manoeuvre can be controlled and the drug release can be adapted to the individual patient; and    9. The reproducibility of the drug release is increased.